PROJECT SUMMARY Patients with gastroparesis often suffer with chronic gastrointestinal symptoms that are not adequately treated due to both a lack of understanding of the underlying pathophysiology and lack of effective treatments. The participation of Temple University as a clinical center in the NIDDK Gastroparesis Clinical Research Consortium and the proposed studies will help achieve the broad, long term objectives of improving the understanding and treatment of patients with gastroparesis. The PI and Temple University are well qualified to continue to be one of the clinical centers in this consortium. Temple University has clinical expertise and an active research program in the evaluation and treatment of patients with gastroparesis. The aims for this renewal of the Gastroparesis Consortium are threefold. First, to better understand the pathologic basis of gastroparesis by continuing to provide gastric full thickness biopsy specimens from patients with gastroparesis. We are now collecting specimens from the antrum and obtaining freshly frozen tissue for RNA expression. Second, to better understand the clinical manifestations and pathophysiology of patients with symptoms of gastroparesis by maintaining and expanding the Gastroparesis Registry. Our goal is to have four years of follow-up on patients which will require maintenance of the Registry and continued periodic follow-up visits. We propose to continue recruitment of new patients. Refinements to existing questionnaires and pathophysiologic measures, as well as new ones, will allow us to answer questions related to the pathogenesis, severity grading, complications, treatment responses, and clinical outcomes in patients with gastroparesis. Third, to conduct new multicenter studies of gastroparesis investigating the pathophysiology, diagnosis, and treatment. Our application proposes three studies, each aimed at the understanding of the pathophysiology of symptoms and treatment of symptoms from gastroparesis. Improved testing will better associate pathophysiology with gastroparesis symptoms and ultimately enable targeted therapy to the underlying gastric pathophysiologic abnormality. Our first study will determine the effect of the 5HT-1 receptor agonist, buspirone, on early satiety and intragastric meal distribution in patients with symptoms of gastroparesis. Our second study is an evaluation of abdominal pain in gastroparesis, determining the prevalence of and response to treatment for chronic pancreatitis. Finally, our third study will assess the clinical outcome of patients undergoing endoscopic pyloromyotomy for gastroparesis, looking at the response and predictive factors for clinical improvement with this novel treatment. These three studies will ultimately enable physicians to better target therapy to the underlying pathophysiologic abnormalities in patients with gastroparesis. Temple's participation in the NIH Gastroparesis Clinical Consortium and the undertaking of Temple's proposed studies will help achieve the goal of the consortium by advancing our understanding of the pathophysiology and developing appropriate treatments for patients with symptomatic gastroparesis.